N-acyl-2-amino acid amides containing phosphinic esters, process for their preparation, and N-acyl-2-amino acids nitriles as precursors

ABSTRACT

N-acyl-2-amino acid amides containing phosphinic esters, process for their preparation, and N-acyl-2-amino acid nitriles as precursors 
     Phosphorus-containing N-acyl-2-amino acid amides of the general formula (I) ##STR1## where R 1  is alkyl, optionally substituted by halogen or alkoxy, or is benzyl or phenyl, each of which is optionally substituted by alkyl, alkoxy, halogen, nitro or CF 3 , or is cycloalkyl, and 
     R 2  is H, or alkyl, optionally substituted by halogen or alkoxy, or is (CH 2 ) n  -phenyl, optionally substituted in the phenyl ring by alkyl, alkoxy, halogen, nitro or CF 3 , where n=0, 1, 2 or 3, 
     are valuable intermediates for the preparation of L-phosphinothricin by enzymatic cleavage, and can be obtained from the corresponding N-acyl-2-amino acid nitrile by selective acid hydrolysis.

Description

N-Acyl-2-amino acid amides containing phosphinic esters, process fortheir preparation, and N-acyl-2-amino acid nitriles as precursors.

The present invention relates to phosphorus-containing N-acyl-2-aminoacid amides of the general formula (I) ##STR2## where R¹ is C₁ -C₁₄-alkyl which is branched or unbranched and unsubstituted ormonosubstituted or polysubstituted by halogen or C₁ -C₆ -alkoxy, or isbenzyl or phenyl, benzyl or phenyl being unsubstituted ormonosubstituted or polysubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl, or is C₃ -C₁₀-cycloalkyl, and

R² is hydrogen, C₁ -C₁₄ -alkyl which is unsubstituted or monosubstitutedor polysubstituted by halogen or C₁ -C₄ -alkoxy, or is a radical of theformula --(CH₂)_(n) -phenyl which is unsubstituted or monosubstituted totrisubstituted in the phenyl ring by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy,halogen, nitro or trifluoromethyl and in which n is 0, 1, 2 or 3.

Compounds of the formula (I) which are of particular interest are thosewhere

R¹ is unbranched or branched C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkyl which ismonosubstituted to trisubstituted by halogen, such as fluorine orchlorine, or is C₅ -C₆ -cycloalkyl, and

R² is hydrogen, unbranched or branched C₁ -C₁₄ -alkyl which isunsubstituted or substituted by one to three radicals from the groupcomprising halogen and C₁ -C₄ -alkoxy, or is a radical of the formula--(CH₂)_(n) -phenyl, the phenyl ring being unsubstituted ormonosubstituted to trisubstituted by halogen and n being 0, 1 or 2.

Preferred compounds of the formula (I) are those where

R¹ is unbranched C₁ -C₈ -alkyl or cyclohexyl, and

R² is C₁ -C₄ -alkyl or benzyl.

Examples of suitable meanings of R¹ are the radicals methyl, ethyl,n-propyl, i-propyl, n-, i-, t- and 2-butyl, n-, i-, t-, 2-, 3- andneo-pentyl, n-, i- and 2-hexyl, heptyl, octyl, nonyl, decyl, undecyl,dodecyl, tridecyl, tetradecyl, 2-chloroethyl, 2,2-dichloroethyl,1,1,2,2-tetrafluoroethyl, 2-methoxyethyl, 1-ethoxyethyl,2,2-dimethoxyethyl, 3-methoxypropyl, benzyl, phenyl, o- and p-tolyl,2-methoxyphenyl, 4-nitrophenyl, 2- or 3-chlorophenyl,4-trifluoromethylphenyl, 4-chlorobenzyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, 4,4-dimethylcyclohexyl, cycloheptyl andcyclooctyl.

Examples of suitable meanings of R² are hydrogen, radicals as listed inthe case of R¹, 1- and 2-phenylethyl, 1-phenylpropyl, 3-phenylpropyl and1-(2-chlorophenyl)ethyl. Halogen in each case is fluorine, chlorineand/or bromine, preferably fluorine and/or chlorine.

The invention also relates to a process for the preparation of thecompounds of the formula (I) according to the invention, which comprisessubjecting N-acyl-2-amino acid nitriles of the formula (II) ##STR3##where R¹ and R² have the meanings indicated in the case of formula (I),to selective acid hydrolysis on the nitrile group to give thecorresponding carboxamide of the general formula (I).

In the compounds of the formulae (I) and (II), there are two centers ofchirality, so that either the mixtures of diastereomers or enantiomersor individual diastereomers or enantiomers of the formula (II) can beemployed in the process according to the invention. The hydrolysis onthe nitrile group proceeds virtually while maintaining the configurationon the two centers of chirality which have been mentioned. If, forexample, an α-D-isomer of the formula (II) is employed which isoptically pure with regard to the center of chirality in the α-positionrelative to the nitrile group and which is only present as a mixture ofstereoisomers with regard to the center of chirality on the phosphinicester group, hydrolysis of the nitrile function according to theinvention gives the α-D-N-acyl-amino acid amide of the general formula(I) while maintaining the configuration (optical activity) with regardto the α-position relative to the nitrile group.

The invention also relates to compounds of the formula (II) which can beused as intermediates for the preparation of the compounds of theformula (I) according to the invention and in which R¹ and R² have themeanings mentioned in the case of formula (I). In formula (II), R¹ andR² preferably have the meanings preferred in the case of formula (I).

The starting materials of the formula (II) which are required forpreparing the compounds of the general formula (I) according to theinvention may be prepared, for example, by acylation of α-amino acidnitriles of the general formula (III) ##STR4## with acid chlorides ofthe formula R² -COCl, or acid anhydrides of the formula (R² CO)₂ O, byprocesses which are generally customary (cf. Organikum [LaboratoryPractice of Organic Chemistry], VEB Deutscher Verlag der Wissenschaften,Berlin 1976, 512 et seq.). The amino acid nitriles of the formula (III)are known from EP-A 194,521 (U.S. Pat. No. 4,692,541) and EP-A 011,245(U.S. Pat. No. 4,521,348), or they can be prepared for example by theprocesses known from these references.

The process according to the invention is carried out in such a way thatcompounds of the formula (II) are selectively hydrolyzed on the nitrilefunction under suitable reaction conditions to give the correspondingcarboxamide of the formula (I), during which process the N-acyl group,or phosphinic ester group, are not attracted or hydrolyzed, or only to anegligible extent. The process is carried out for example in formicacid, if appropriate in the presence of Lewis acids, such as hydrogenhalides, for example hydrogen chloride or hydrogen bromide, ifappropriate in the presence of an inert organic solvent, such as, forexample, dichloromethane, toluene or chlorobenzene. Analogous reactionconditions are known from Liebigs Annalen der Chemie 713, 212 (1968);loc. sit. 749, 198 (1971); J. Chem. Soc. [C], 1970, 1230. Formic acidcan be employed in 100% pure form or in a lower concentration, i.e.,diluted with water. Formic acid is employed in amounts of 90 to 600mol-%, preferably in equimolar amounts or a 2- to 3-fold excess, basedon the compound of the formula (II).

The process according to the invention is preferably carried out atreaction temperatures of 0°-260° C., in particular at below 250° C., andunder pressure using formic acid without Lewis catalysts, or at 0°-60°C. using formic acid in the presence of Lewis catalysts. The Lewis acidsare generally employed in catalytic amounts, for example 0.1 to 2 mol-%,preferably about 0.5 mol-%, or, alternatively, in excess, for example150 to 600 mol-%.

Depending on the reaction conditions, the duration of the reaction canvary within wide limits, but it is generally 0.1 to 48 hours, preferably0.5 to 6 hours.

The preparation process according to the invention for compounds of theformula (I) is surprisingly selective. The N-acyl-2-amino acid nitrilesof the general formula (II) are selectively cleaved to give theN-acyl-amino acid amides of the general formula (I), in which processfor example the acid-labile phosphinic ester group or the N-acyl group,which can likewise be cleaved under acid conditions, are attacked to anegligible extent only. DE-A 2,717,440 (GB-A-1,587,292) or EP-A 011,245disclose processes according to which for example ethyl3-amino-3-cyano-propyl(methyl)phosphinate, prepared in a Streckersynthesis, is cleaved completely using hydrochloric acid to give thecorresponding 3-amino-3-carboxy-propyl(methyl)phosphinic acid. FromLiebigs Ann. Chem. 749, 198 (1971) it is known that dimethyl(2-cyanoethyl)phosphonate is cleaved in formic acid/hydrogen chloride togive (2-amidocarbonylethyl)phosphonic acid, during which process partialhydrolysis to give monomethyl or dimethyl(2-amidocarbonylethyl)phosphonate obviously does not take place.Compared with this process, the process according to the inventionpermits carboxamides containing phosphinic esters, of the generalformula (I), to be prepared in almost quantitative yields, i.e.,virtually without hydrolysis on the phosphinic ester group.

The N-acyl-α-amino acid amides of the general formula (I) are valuableprecursors which can be cleaved enzymatically to give L-phosphinothricinwith high excesses of enantiomers (cf. German Patent Application P3903446.1, HOE 89/F 042). L-Phosphinothricin has bactericidal (Helv.Chim. Acta. 55, 224 (1972)), fungicidal (Sci. Rep. Meiji Seika Kaisha13, 34 (1973)) and excellent herbicidal properties (DE-A 2,717,440, EP-A54,897).

The examples below are intended to illustrate the invention in greaterdetail without restricting it to the concrete examples.

EXAMPLE 1

CyclohexylD,L-(3-phenylacetamido-3-aminocarbonylpropyl)methylphosphinate

(a) Cyclohexyl D,L-(3-acetoxy-3-cyanopropyl)methylphosphinate(preparation analogously to EP-11,245); 50 g (0.4 mol) ofacroleincyanohydrin acetate which contains 4 g of t-butyl peroctoate areadded dropwise within 1 hour at 120° C. under a nitrogen atmosphere to130 g (0.8 mol) of monocyclohexyl methanephosphonite. When the dropwiseaddition is complete,stirring is continued at 120° C. for 15 minutes,and the mixture is subsequently subjected to fractional distillationunder reduced pressure. This gives 106 g (92% of theory) of cyclohexylD,L-(3-acetoxy-3-cyanopropyl)methylphosphinate of boiling point 178° to180° C. at 0.02 mbar.

(b) Cyclohexyl D,L-(3-phenylacetamido-3-cyanopropyl)methylphosphinate;28.7g (0.1 mol) of cyclohexylD,L-(3-acetoxy-3cyanopropyl)methylphosphinate areadded dropwise at 20°C. within 1 hour to 29.6 ml of concentrated ammonia. The reactionmixture is subsequently extracted using methylene chloride, and theextract is dried over sodium sulfate and treated with 10.2 g (0.1 mol)of triethylamine. 15.4 g (0.1 mol) of phenylacetyl chloride are addeddropwise at 0° C. After the mixture has been stirred for 18 hours atroom temperature, it is treated with 50 ml of water, a pH of 5 isestablished using 0.5 N hydrochloric acid, and the mixture is extractedusing methylene chloride. The oil which remains afterthe methylenechloride extract has been evaporated off is purified by chromatographyon silica gel (mobile phase: methylene chloride). This gives 27.5 g (76%of theory) of cyclohexyl D,L-(3-acetoxy-3-cyanopropyl)methylphosphinate;¹ H-NMR (CDCl₃): δ=9.45 (NH, m, 1H); 7.3 (C₆ H₅, s, 5H); 4.95 (CH, m,1H); 4.36 (CH, m, 1H); 3.6 (CH₂, s, 2H); 1.2-2.2 (CH₂ CH₂, PCH₃, C₆ H₁₀,m, 17H).

(c) CyclohexylD,L-(3-phenylacetamido-3-aminocarbonylpropyl)methylphosphinate; 6 g(0.01 mol) of cyclohexylD,L-(3-phenylacetamido-3-cyanopropyl)methylphosphinate are dissolved in40 ml of formic acid. After this, HCl gas is passed in atroomtemperature. After 3 hours, the reaction mixture is concentrated, theresidue is dissolved in methylene chloride and water, and the pH of 5 isestablished using sodium hydrogen carbonate. After the mixture has beenextracted using methylene chloride, the methylene chloride extracts aredried over sodium sulfate and subjected to evaporation on a rotaryevaporator. The crude product which remains is purified bychromatography on silica gel (mobile phase: methylene chloride/methanol9:1). This gives 5.90 g (94.1% of theory) of a pale yellow oil; ¹ H-NMR(CDCl₃): δ=7.2 (C₆ H₅, s, 5H); 7.2 (CONH₂, d, 2H); 5.6 (NH, s,1H);4.2-4.8 (2×CH, m, 2H); 3.6 (Ch₂, s, 2H); 1.2-2.3 (CH₂CH₂, PCH₃, C₆ H₁₀,m, 17H).

After some weeks, the substance crystallizes to give afinely-crystalline, colorless powder of a melting point 128° to 130° C.

Examples 2(b) to 50(b)

The compounds of the general formula (II) which are mentioned in Table 1below may be prepared analogously to the N-acyl-α-amino acidnitriledescribed in Example 1(b).

                  TABLE 1                                                         ______________________________________                                         ##STR5##                     (II)                                            Ex.                                                                           No.  R.sup.1     R.sup.2        mp     n.sub.D.sup.20                         ______________________________________                                         2b  CH.sub.3    CH.sub.3       resin                                          3b  C.sub.2 H.sub.5                                                                           CH.sub.3                                                      4b  n-C.sub.3 H.sub.7                                                                         CH.sub.3                                                      5b  i-C.sub.3 H.sub.7                                                                         CH.sub.3              1.4600                                  6b  n-C.sub.4 H.sub.9                                                                         CH.sub.3                                                      7b  i-C.sub.4 H.sub.9                                                                         CH.sub.3       40-42° C.                               8b  sec.-C.sub.4 H.sub.9                                                                      CH.sub.3                                                      9b  n-C.sub.5 H.sub.11                                                                        CH.sub.3                                                     10b  i-C.sub.5 H.sub.11                                                                        CH.sub.3                                                     11b  n-C.sub.6 H.sub.13                                                                        CH.sub.3                                                     12b  Cyclopentyl CH.sub.3              1.4280                                 13b  Cyclohexyl  CH.sub.3                                                     14b  n-C.sub.7 H.sub.15                                                                        CH.sub.3                                                     15b  n-C.sub.8 H.sub.17                                                                        CH.sub.3                                                     16b  ClC.sub.2 H.sub.4                                                                         CH.sub.3                                                     17b  CH.sub.3    Benzyl         resin                                         18b  C.sub.2 H.sub.5                                                                           "                                                            19b  n-C.sub.3 H.sub.7                                                                         "                                                            20b  i-C.sub.3 H.sub.7                                                                         "              resin                                         21b  n-C.sub.4 H.sub.9                                                                         "                                                            22b  i-C.sub.4 H.sub.9                                                                         "              resin                                         23b  sec.-C.sub.4 H.sub.9                                                                      "                                                            24b  n-C.sub.5 H.sub.11                                                                        "                                                            25b  i-C.sub.5 H.sub.11                                                                        "                                                            26b  n-C.sub.6 H.sub.13                                                                        "                                                            27b  Cyclopentyl "                                                            28b  CH.sub.3    C.sub.2 H.sub.5                                              29b  C.sub.2 H.sub.5                                                                           "                                                            30b  n-C.sub.3 H.sub.7                                                                         "                                                            31b  i-C.sub.4 H.sub.9                                                                         "                                                            32b  Cyclohexyl  "                                                            33b  Cyclopentyl "                                                            34b  ClCH.sub.2 CH.sub.2                                                                       C.sub.2 H.sub.5                                              35b  CH.sub.3 OCH.sub.2 CH.sub.2                                                               CH.sub.3                                                     36b  C.sub.6 H.sub.5                                                                           CH.sub.3                                                     37b  CH.sub.2 C.sub.6 H.sub.5                                                                  CH.sub.3                                                     38b  4-NO.sub.2C.sub.6 H.sub.4                                                                 CH.sub.3                                                     39b  2-ClC.sub.6 H.sub.4                                                                       CH.sub.3                                                     40b  Cyclohexyl  CH.sub.2 CH.sub.2 C.sub.6 H.sub.5                            41b  CH.sub.3    "                                                            42b  i-C.sub.3 H.sub.7                                                                         "                                                            43b  CH.sub.3    C.sub.6 H.sub.5                                              44b  Cyclohexyl  "                                                            45b  CH.sub.3    2-ClC.sub.6 H.sub.4                                          46b  CH.sub.3    p-Tolyl                                                      47b  CH.sub.3    2,4-Cl.sub.2C.sub.6 H.sub.4                                  48b  CH.sub.3    3-OCH.sub.3C.sub.6 H.sub.4                                   49b  CH.sub.3    4-CH.sub.2C.sub.6 H.sub.4CH.sub.2                            50b  CH.sub.3    2-ClC.sub.6 H.sub.4CH.sub.2                                  ______________________________________                                    

Examples 2(c) to 50(c)

For example, the compounds of the general formula (I) listed in Table 2maybe prepared analogously to the N-acyl-α-amino acid amide describedinExample 1(c).

                  TABLE 2                                                         ______________________________________                                         ##STR6##                     (I)                                             Ex.                                                                           No.  R.sup.1     R.sup.2        mp     n.sub.D.sup.20                         ______________________________________                                         2c  CH.sub.3    CH.sub.3       resin                                          3c  C.sub.2 H.sub.5                                                                           CH.sub.3                                                      4c  n-C.sub.3 H.sub.7                                                                         CH.sub.3                                                      5c  i-C.sub.3 H.sub.7                                                                         CH.sub.3              1.4622                                  6c  n-C.sub.4 H.sub.9                                                                         CH.sub.3                                                      7c  i-C.sub.4 H.sub.9                                                                         CH.sub.3       126-170                                        8c  sec.-C.sub.4 H.sub.9                                                                      CH.sub.3                                                      9c  n-C.sub.5 H.sub.9                                                                         CH.sub.3                                                     10c  i-C.sub.5 H.sub.9                                                                         CH.sub.3                                                     11c  n-C.sub.6 H.sub.11                                                                        CH.sub.3                                                     12c  Cyclopentyl CH.sub.3       164-165                                       13c  Cyclohexyl  CH.sub.3       85-86                                         14c  n-C.sub.7 H.sub.15                                                                        CH.sub.3                                                     15c  n-C.sub.8 H.sub.17                                                                        CH.sub.3                                                     16c  ClC.sub.2 H.sub.4                                                                         CH.sub.3       44-45                                         17c  CH.sub.3    Benzyl                                                       18c  C.sub.2 H.sub.5                                                                           "              resin                                         19c  n-C.sub.3 H.sub.7                                                                         "                                                            20c  i-C.sub.3 H.sub.7                                                                         "                                                            21c  n-C.sub.4 H.sub.9                                                                         "                                                            22c  i-C.sub.4 H.sub.9                                                                         "                                                            23c  sec.-C.sub.4 H.sub.9                                                                      "                                                            24c  n-C.sub.5 H.sub.11                                                                        "                                                            25c  i-C.sub.5 H.sub.11                                                                        "                                                            26c  n-C.sub.6 H.sub.13                                                                        "                                                            27c  Cyclopentyl "                                                            28c  CH.sub.3    C.sub.2 H.sub.5                                              29c  C.sub.2 H.sub.5                                                                           "                                                            30c  n-C.sub.3 H.sub.7                                                                         "                                                            31c  i-C.sub.4 H.sub.9                                                                         "                                                            32c  Cyclohexyl  "                                                            33c  Cyclopentyl "                                                            34c  ClCH.sub.2 CH.sub.2                                                                       C.sub.2 H.sub.5                                              35c  CH.sub.3 OCH.sub.2 CH.sub.2                                                               CH.sub.3                                                     36c  C.sub.6 H.sub.5                                                                           CH.sub.3                                                     37c  CH.sub.2 C.sub.6 H.sub.5                                                                  CH.sub.3                                                     38c  4-NO.sub.2C.sub.6 H.sub.4                                                                 CH.sub.3                                                     39c  2-ClC.sub.6 H.sub.4                                                                       CH.sub.3                                                     40c  Cyclohexyl  CH.sub.2 CH.sub.2 C.sub.6 H.sub.5                            41c  CH.sub.3    "                                                            42c  i-C.sub.3 H.sub.7                                                                         "                                                            43c  CH.sub.3    C.sub.6 H.sub.5                                              44c  Cyclohexyl  "                                                            45c  CH.sub.3    2-ClC.sub.6 H.sub.4                                          46c  CH.sub.3    p-Tolyl                                                      47c  CH.sub.3    2,4-Cl.sub.2C.sub.6 H.sub.4                                  48c  CH.sub.3    3-OCH.sub.3C.sub.6 H.sub.4                                   49c  CH.sub.3    4-CH.sub.2C.sub.6 H.sub.4CH.sub.2                            50c  CH.sub.3    2-ClC.sub.6 H.sub.4CH.sub.2                                  ______________________________________                                    

I claim:
 1. An N-acyl- 2-amino acid amide of the formula (I) ##STR7##where R¹ is C₁ -C₁₄ -alkyl which is branched or unbranched andunsubstituted or monosubstituted or polysubstituted by halogen or C₁ -C₆-alkoxy, or is benzyl or phenyl, benzyl or phenyl being unsubstituted ormonosubstituted or polysubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl, or is C₃ -C₁₀-cycloalkyl, andR² is hydrogen, C₁ -C₁₄ -alkyl which is unsubstituted ormonosubstituted or polysubstituted by halogen or C₁ -C₄ -alkoxy, or is aradical of the formula --(CH₂)_(n) -phenyl which is unsubstituted ormonosubstituted to trisubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl and in which n is 0,1, 2 or 3,with the proviso that R¹ is not ethyl when R² is methyl.
 2. Acompound of the formula (I) as claimed in claim 1, whereinR¹ isunbranched or branched C₁ -C₁₀ -alkyl or C₁ -C₁₀ -alkyl which ismonosubstituted to trisubstituted by halogen, or is C₅ -C₆ -cycloalkyl,and R² is hydrogen, unbranched or branched C₁ -C₁₄ -alkyl which isunsubstituted or substituted by one to three radicals from the groupcomprising halogen and C₁ -C₄ -alkoxy, or is a radical of the formula--(CH₂)_(n) --phenyl, the phenyl ring being unsubstituted ormonosubstituted to trisubstituted by halogen and n being 0, 1 or
 2. 3. Acompound of the formula (I) as claimed in claim 1, whereinR¹ isunbranched C₁ -C₈ -alkyl or cyclohexyl, and R² is C₁ -C₄ -alkyl orbenzyl.
 4. A compound of the formula (II) ##STR8## wherein R¹ is C₁ -C₁₄-alkyl which is branched or unbranched and unsubstituted ormonosubstituted or polysubstituted by halogen or C₁ -C₆ -alkoxy, or isbenzyl or phenyl, benzyl or phenyl being unsubstituted ormonosubstituted or polysubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl, or is C₃ -C₁₀-cycloalkyl, andR² is a radical of the formula --(CH₂)_(n) -phenyl whichis unsubstituted or monosubstituted to trisubstituted in the phenyl ringby C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl andin which n is 0, 1, 2 or
 3. 5. A compound of the formula II as claimedin claim 4, whereR¹ is unbranched or branched C₁ -C₁₀ -alkyl or C₁ -C₁₀-alkyl which is monosubstituted to trisubstituted by halogen, or is C₅-C₆ -cycloalkyl, and R² is a radical of the formula --(CH₂)_(n) -phenyl,the phenyl ring being unsubstituted or monosubstituted to trisubstitutedby halogen and n being 0, 1 or
 2. 6. A compound as claimed in claim 4,whereinR¹ is unbranched C₁ -C₈ -alkyl or cyclohexyl, and R² is benzyl.7. A process for the preparation of a compound of the formula (I)##STR9## where R¹ is C₁ -C₁₄ -alkyl which is branched or unbranched andunsubstituted or monosubstituted or polysubstituted by halogen or C₁ -C₆-alkoxy, or is benzyl or phenyl, benzyl or phenyl being unsubstituted ormonosubstituted or polysubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl, or is C₃ -C₁₀-cycloalkyl, andR² is hydrogen, C₁ -C₁₄ -alkyl which is unsubstituted ormonosubstituted or polysubstituted by halogen or C₁ -C₄ -alkoxy, or is aradical of the formula --(CH₂)_(n) -phenyl which is unsubstituted ormonosubstituted to trisubstituted in the phenyl ring by C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, halogen, nitro or trifluoromethyl and in which n is 0,1, 2 or 3,which comprises subjecting an N-acyl-2-amiano acid nitrile ofthe formula (II) ##STR10## where R¹ and R² have the meanings indicatedin the case of formula (I), to selective acid hydrolysis on the nitrilegroup, to give the corresponding carboxamide of the formula (I).
 8. Theprocess as claimed in claim 7, in which the hydrolysis is carried out informic acid or aqueous formic acid.
 9. The process as claimed in claim7, in which the hydrolysis is carried out using formic acid in thepresence of hydrogen halide.
 10. The process as claimed in claim 7, inwhich a solvent is used which is inert under the reaction conditions.11. The process as claimed in claim 7, in which the hydrolysis iscarried out at 0° to 250° C.